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Updated: Jun 13, 2025

Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
Published on: March 26, 2019
Microglia contact cerebral vasculature through gaps between astrocyte endfeet
Gary P Morris1, Catherine G Foster1,2, Brad A Sutherland1
1Tasmanian School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia.
Abstract:
The close spatial relationship between microglia and cerebral blood vessels implicates microglia in vascular development, homeostasis and disease. In this study we used the publicly available Cortical MM^3 electron microscopy dataset to systematically investigate microglial interactions with the vasculature. Our analysis revealed that approximately 20% of microglia formed direct contacts with blood vessels through gaps between adjacent astrocyte endfeet. We termed these contact points "plugs". Plug-forming microglia exhibited closer proximity to blood vessels than non-plug forming microglia and formed multiple plugs, predominantly near the soma, ranging in surface area from ∼0.01 μm2 to ∼15 μm2. Plugs were enriched at the venule end of the vascular tree and displayed a preference for contacting endothelial cells over pericytes at a ratio of 3:1. In summary, we provide novel insights into the ultrastructural relationship between microglia and the vasculature, laying a foundation for understanding how these contacts contribute to the functional cross-talk between microglia and cells of the vasculature in health and disease.
Insights
Microglia directly contact cerebral blood vessels through "plugs" at gaps between astrocyte endfeet. These findings reveal novel microglial-vascular interactions crucial for brain health and disease.
Area of Science:
- Neuroscience
- Cell Biology
- Vascular Biology
Background:
- Microglia, the brain's resident immune cells, have a close spatial relationship with cerebral blood vessels.
- This proximity suggests a role for microglia in vascular development, homeostasis, and disease processes.
Purpose of the Study:
- To systematically investigate microglial interactions with the vasculature using high-resolution electron microscopy data.
- To characterize the nature and extent of direct contacts between microglia and cerebral blood vessels.
Main Methods:
- Utilized the publicly available Cortical MM^3 electron microscopy dataset.
- Systematically analyzed microglial ultrastructure and spatial relationships with cerebral vasculature.
- Quantified microglial-blood vessel contact points, termed "plugs".
Main Results:
- Approximately 20% of microglia formed direct contacts with blood vessels via "plugs" through astrocyte endfeet gaps.
- Plug-forming microglia were in closer proximity to vessels and formed multiple plugs, primarily near their soma.
- Plugs were more frequent at venules and contacted endothelial cells over pericytes (3:1 ratio).
Conclusions:
- Novel insights into the ultrastructural relationship between microglia and the cerebral vasculature were provided.
- The study identified specific microglial contact points ("plugs") with blood vessels.
- These findings lay the foundation for understanding microglial-vascular cross-talk in neurological health and disease.
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